The objective of this proposal is to study the effect of three different insulin treatment regimens on the development of diabetic nephropathy in the alloxan diabetic dog. The four groups will be: (1) diabetic with prospective good conventional plasma glucose control; (2) diabetic with prospective poor conventional control; (3) diabetic with continuous modulated infusion from an implanted pump; and, (4) nondiabetic. We are currently funded to perform the above experiment using uninephrectomized dogs which are expected to develop nephropathic lesions in a relatively short time. The early manifestation of diabetic kidney lesions in some dogs, examined by us, suggested detectable angiopathy will occur much sooner than we originally thought allowing us to conclude the study of uninephrectomized animals sooner than planned. We are, thus, requesting additional funds to run a second experiment of intact animals during the remainder of the grant period after the work with uninephrectomy is completed.